Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders

Abstract

Autism Spectrum Disorders (ASD) are a group of heterogeneous, behaviorally defined disorders characterized by disturbances in social interaction and communication, often with repetitive and stereotyped behavior. Previous studies have described the presence of antibodies to various neural proteins in autistic individuals as well as post-mortem evidence of neuropathology in the cerebellum. We examined plasma from children with ASD, as well as age-matched typically developing controls, for antibodies directed against human cerebellar protein extracts using western blot analysis. In addition, the presence of cerebellar specific antibodies was assessed by immunohistochemical staining of sections from Macaca fascicularis monkey cerebellum. Western blot analysis revealed that 13/63 (21%) of subjects with ASD possessed antibodies that demonstrated specific reactivity to a cerebellar protein with an apparent molecular weight of approximately 52kD compared with only 1/63 (2%) of the typically developing controls (p=0.0010). Intense immunoreactivity, to what was determined morphologically to be the Golgi cell of the cerebellum, was noted for 7/34 (21%) of subjects with ASD, compared with 0/23 of the typically developing controls. Furthermore, there was a strong association between the presence of antibodies reactive to the 52 kDa protein by western blot with positive immunohistochemical staining of cerebellar Golgi cells in the ASD group (r= 0.76; p=0.001) but not controls. These studies suggest that when compared with age-matched typically developing controls, children with ASD exhibit a differential antibody response to specific cells located in the cerebellum and this response may be associated with a protein of approximately 52 kDa.

The Role of the Immune System in Autism Spectrum Disorder

“…A similar result found that children with autism showed positive serum anti-brain reactivity against prenatal rat proteins by western blot, with a different set of banding patterns relative to their non-autistic siblings and other controls (Zimmerman et al, 2007). A 2009 study of plasma from 63 young children with ASD found that 21% of them had antibodies positive against both human and macaque cerebellum samples via western blot, while only one out of the 63 typical developing (TD) controls (2%) tested positive (Wills et al, 2009). When a subset of subject samples was examined via immunohistochemistry (IHC), 21% of those from children with ASD had 'intense immunoreactivity' while none of the TD controls exhibited such reactivity.…”

Gastrointestinal Conditions in Children With Autism Spectrum Disorder: Developing a Research Agenda

“…[25][26][27][28] Among the most common findings in ASD subjects and their mothers is an increased presence of autoantibodies directed toward central nervous system proteins. [29][30][31][32][33] In addition, autoantibodies that bind to basement membranes of epithelial cells and colocalize with complement proteins are observed in the intestinal mucosa of children with ASD and GI symptoms. 34 It has been speculated that these autoantibodies could indicate the presence of inflammatory processes and/or an autoimmune component that could affect the integrity of the mucosal barrier and contribute to decreased mucosal barrier integrity; it is also possible that they indicate previous mucosal inflammation.…”

Nicotinic Acetylcholine Receptor Alterations in Autism Spectrum Disorders – Biomarkers and Therapeutic Targets

“…Lastly, there is accumulating evidence that the immune system is disrupted in individuals with ASD (Careaga et al, 2010). Elevated levels of chemokines have been detected in the brains and cerebrospinal fluid (Chez et al, 2007;Wills et al, 2009) as well as the plasma (Ashwood et al, 2011a) of individuals with ASD, and this elevation correlated with more impaired behavior (Ashwood et al, 2011b). Furthermore, postmortem studies of individuals with autism also detected presence of activated neuroglial cells in their brain (Vargas et al, 2005).…”